Program Director/Principal Investigator (Last, First, Middle): Khush, Kiran Kaur PROJECT SUMMARY(Seeinstructions): This is an application for a K23 awardfor Dr. Kiran Khush, an instructor in cardiology and heart transplantation at Stanford University, who is establishing herself as a young investigator studying donor evaluation for heart transplantation. This K23 award will provide Dr. Khush with the support necessary to accomplish the following goals: (1) to independently design, implement, and analyze cohort study data; (2) to obtain fluency in biostatistical methodology and genetic epidemiology; and (3) to develop an independent clinical research career. To achieve these goals, Dr. Khush will work closely with her primary mentor Dr. Hannah Valantine, Director of Heart Transplant Research at Stanford, and her co-mentor Dr. Thomas Quertermous, Research Chief of the Division of Cardiovascular Medicine at Stanford. Dr. Valantine has extensive clinical research experience within the realm of heart transplantation and has a proven track record of successfully mentoring junior faculty. Dr. Quertermous is an internationally-recognized expert in cardiovascular genetics and has guided many junior faculty members towards independent careers. Heart transplantation provides the most effective treatment for end-stage heart disease. The critical deficit in suitable donor hearts, however, continues to limit transplant rates in the United States and worldwide. One solution to the donor shortage is to increase the yield of acceptable hearts from available donors through development of systematic, evidence-based criteria for donor selection. Dr. Khush will leverage the resources available at Stanford University to identify clinical and genetic risk factors for graft left ventricular dysfunction (Aim 1), to identify donor clinical and genetic predictors of poor recipient outcomes after transplantation (Aim 2), and to perform a prospective cohort study evaluating whether early post-transplant biomarkers mediate the associations between donor risk factors and recipient outcomes. This research will provide Dr. Khush with the skills and preliminary data necessary to investigate the mechanisms that modulate recipient outcomes after heart transplantation, to be proposed in an R01 grant application before the end of the K award period. RELEVANCE (See instructions): Approximately 60% of potential donor hearts are discarded, primarily due to left ventricular dysfunction. Understanding the mechanisms responsible for graft dysfunction may facilitate the development of prevention or treatment strategies to increase the availability of donor hearts. Moreover, systematic evaluation of donor risk factors for adverse post-transplant outcomes may help to refine current donor selection criteria.